Chemical compounds and methods of preparing the same

ABSTRACT

THE DISCLOSURE DECRIBES DERIVATIVES OF DIBENZOCYCLOHEPTENSES USEFUL BECAUSE OF THEIR ANTIDEPRESSANT ACTIVITY. THE DISCLOSURE ALSO DESCRIBES A METHOD FOR PREPARING THESE COMPOUNDS FROM THE KNOWN 3A, 12B-DIHYDRO-2-2-DIMETHYL - 5H -DIBENZO (3,4:6,7) CYCLOHEPTA (1,2-D) -1,3- DIOXOL-8-ONE AND DERIVATIVES THEREOF WHICH CONTAIN ADDITIONAL SUBSTITUENTS SUBSTITUTED IN ANY POSITION OF THE BENZEN0ID RING. THIS STARTING MATERIAL, ALTERNATIVELY KNOWN AS THE ACETONIDE OF 10,11-DIHYDROXY-10,11-DIHYDRO-5H-DIBENZO-(A,D)-CYCLOHEPTEN-5-ONE IS CONVERTED BY TREATMENT WITH A 3-DIALKYLAMINOPROPYL MAGNESIUM HALIDE TO PRODUCE THE CORRESPONDING 5-HYDROXY - 5 -(3-DIALKLAMINOPROPY) COMPOUND WHICH IS THEN DEHYDRATED UNDER ACIDIC CONDITIONS TO PRODUCE THE ACETONIDE OF 10,11-DIHYDROXY-10-11DIHYDRO-5-(3-DIALKYLAMINOPROPYLIDENE)-5H-DIBENZO(A,D) CYCLOHEPTENE. THIS PRODUCT IS HYDROLYZED TO PRODUCE THE CORRESPONDING 10,11-DIHYDROXY -5- (3-ALKYLAMINOPROPYLIDENE)-5H-DIBENZO(A,D) CYCLOHEPTENE.

United States Patent CHEMICAL COMPOUNDS AND METHODS OF PREPARING THE SAME Marcia E. Christy, Perkasie, Pa., assignor to Merck 8: Co., Inc., Rahway, NJ.

No Drawing. Original application Jan. 29, 1968 Ser. No. 723,964, now Patent No. 3,576,823. Divided and this application June 22, 1970, Ser. No. 48,475

Int. Cl. (107d 21/00 US. Cl. 260-3405 11 Claims ABSTRACT OF THE DISCLOSURE The disclosure describes derivatives of dibenzocycloheptenes useful because of their antidepressant activity. The disclosure also describes a method for preparing these compounds from the known 3a,l2fi-dihydro-2,2-di methyl 5H dibenzo[3,4:6,7]cyclohepta[1,2-d] 1,3 dioxol-8-one and derivatives thereof which contain additional substituents substituted in any position of the benzenoid ring. This starting material, alternatively known as the acetonide of 10,11-dihydroxy-10,1l-dihydro-SH-dibenzo-[a,d]-cyclohepten-S-one is converted by treatment with a 3-dialkylaminopropyl magnesium halide to produce the corresponding zi-hydroxy 5 (S-dialkylaminopropyl) compound which is then dehydrated under acidic conditions to produce the acetonide of 10,11dihydroxy-l0,11- dihydro-S- 3 dialkylaminopropylidene -5H-dibenzo [a,d] cycloheptene. This product is hydrolyzed to produce the corresponding 10,11-dihydroxy 5 (B-alkylaminopropylidene -5H-dibenzo [a,d] cycloheptene.

HO OH wherein R is a lower alkyl radical, straight or branched chain, preferably having up to 6 carbon atoms; R is a lower alkyl radical, straight or branched chain, preferably having up to 6 carbon atoms and X and X, which may be similar or dissimilar, are hydrogen, an alkyl group having up to 6 carbon atoms, an alkenyl group having up to 6 carbon atoms, halogen, trifluoromethyl, hydroxyl, an alkoxy group having up to 4 carbon atoms, mercapto, an alkylmercapto group having up to 4 carbon atoms, an alkylsulfonyl group having up to 4 carbon atoms, sulfamoyl, an alkylsulfamoyl group having up to 4 carbon atoms or a dialkylsulfamoyl group having up to 8 carbon atoms.

3,720,688 Patented Mar. 13, 1973 More than one of these substituents may be on each of the benzenoid rings. The radicals R and R may be similar or dissimilar and they may be linked together through an atom of carbon, nitrogen or oxygen to form a heterocyclic ring having from five to six atoms therein such as l-piperidyl, l-pyrrolidyl, 4-morpholinyl and 1-lower alkyl- 4-piperazinyl, the lower alkyl substituent of the latter preferably having up to 4 carbon atoms.

The compounds represented by the above structural formulae may also have substituents on the propylidene side chain such as. lower alkyl radicals, preferably having from 1 to 4 carbon atoms.

Representative end compounds encompassed Within the scope of the present invention include:

i0,1 1-dihydro-10,11-dihydroxy-5-[3-( 1-piperidy1)-propylidene] -5H-dibenzo [a,d] cycloheptene 10,11-dihydro-10,1l-dihydroxy-5-[3-(1-methyl-4-piperazinyl )-propylidene] -5H-dibenzo [a,d] cycloheptene 10,1 1-dihydro-1 0,1 1-dihydroxy-5-( 3-dimethylaminopropylidene -5H-dibenzo [a,d] cycloheptene 10, 1 1-dihydro-10,1 l-dihydroxy-S- 3-methylaminopropylidene -5H-dibenzo[a,d] cycloheptene 3-chloro-l 0,1 l-dihydro- 10,1 1-dihydroXy-5- S-dimethylaminopropylidene -5H-dibenzo a,d] cycloheptene 10, 1 1-dihydro-10,1 l-dihydroxy-S- (3-methylaminopropylidene -3-methylsulfonyl-SH-dibenzo[a,d] cycloheptene 1 0, 1 1-dihydro-10,1 l-dihydroxy-S- S-dimethylaminopropylidene -3-trifiuorornethyl-SH-dibenzo [a,d] cycloheptene 10,1 l-dihydro- 10,1 l-dihydroxy-S-(3-diethy1aminopropylidene) -3-dimethylsulfamoyl-SH-dibenzo [a,d] cycloheptene The compounds represented by the above structural formulae can advantageously be employed in pharmaceutical applications because they have been found to possess antidepressant activity. As anti-depressants, they maybe administered orally in the form of tablets, powders, sustained release pellets and the like, or they may be administered orally or parenterally in the form of aqueous solutions or suspensions. When administered orally or parenterally, satisfactory results are obtained at a daily dosage level of from about 60 mg. to about 1,000 mg., preferably given in divided doses over the day or in sustained. release form. The compounds are preferably administered in the form of their non-toxic acid addition salts and these salts are included within the scope of this invention.

The compounds represented by the above structural formulae exist as geometric isomers, which are determined by the steric relationships of the hydroxyl groups to each other. In order to prepare the separate isomers, it is necessary to employ an appropriate starting material in the same isomeric form as that desired of the end product. Thus, where it is desired to prepare the trans isomer of the compounds represented structurally above, a trans 301,12}? dihydro 8H-dibenzo[3,4:6,7]cyclohepta- [1,2-d]-1,3-dioxol-8-one is employed, whereas the cis isomers are prepared starting with a cis 10,11-dihydro-10,1ldiacyloxy-SH-dibenzo [a,d] cyclohepten-S-one.

' In carrying out the process, the desired ketone is treated with a Grignard reagent, namely, a tertiary aminopropyk magnesium halide and the Grignard adduct obtained hydrolyzed to form the corresponding S-hydroxy-S-(S-tertiary aminopropyl) derivative. This is then dehydrated to form the corresponding 5-(3-tertiary aminopropylidene) derivative, which is then either hydrolyzed to form the cis or trans 10,11-dihydroxy compounds represented by structural Formula I or dealkylated and then hydrolyzed to form the cis or trans 10,11-dihydroxy compounds represented by structural Formula II.

The process for the preparation of the trans 10,11-dihydroxy compounds represented by structural Formula I may be illustrated as follows:

RI! RI/I C 2\ 1 30 123 1. HalMgCHzCHzCHzN /1-2 |A2b 3a 4 11 R X-- -X' a Ci Hydrolysis 9 8 7 Step A RI! RH! X t l HO CHzCIIgCHzN RI Dehydration Step B H drol sis y y X X, Step C l It CHCHzCHzN HO (|)H X I X /R UIICII CH N wherein Hal represents halogen, preferably chlorine or bromine and X, X, R and R are as previously defined; and R and R are hydrogen, alkyl, aralkyl or aryl.

The starting compound, wherein X and X are both hydrogen and R and R' are both methyl, namely, the 30:,125 dihydro 2,2 dimethyl-SH-dibenzo[3,4:6,7]- cyclohepta[l,2-d]-1,3-dioxol-8-one, may be prepared in the manner described by G. L. Buchanan and D. B. Jhaveri in the J. Org. Chem. 26, 4295-4299 (1961). Those starting compounds, wherein at least one of X and X is other than hydrogen, may be prepared from the corresponding nuclearly substituted H dibenzo[a,d]- cyclohepten-5-one utilizing the procedure of G. L. Buchanan and D. B. Jhaveri, referred to above. The latter compounds may be prepared following the teachings of T. W. Campbell et al. in an article appearing in Helv. Chem. Acta, vol. 36, pages 1489-1499 (1953).

Those starting compounds, wherein R" and R are other than methyl, may be prepared from the corresponding diol by treatment with an appropriate aldehyde or ketone utilizing the procedure described by G. L. Buchanan and D. B. Jhaveri for the preparation of the acetonide of the trans diol appearing in the article referred to above.

It should be noted that inasmuch as the R" and R substituents are removed during the preparation of the end compounds of this invention, the selection of the particular starting compound with respect to these sub- 4 stituents will be dependent only upon their ease of preparation and the removal of the R and R substituents during subsequent hydrolysis.

The Grignard reagent employed in Step A of the above process may be prepared by known procedures, but it has been found that it may be prepared in high yields as follows:

tetrahydrol'uran Mg HalCHzCHzCHaN R HalMgCHzCHzCHzN 'It has been found that the use of tetrahydrofuran as the solvent for the reaction results in a rapid production of the Grignard reagent in high yield.

The reaction with the Grignard reagent (Step A) is preferably initially carried out under cooled conditions such as by the use of an ice-bath, and finally may continue at room temperature. It has been found that tetrahydrofuran is a suitable solvent for carrying out the reaction and, accordingly, the ketone may be added directly to the reaction mixture in which the Grignard reagent was prepared. However, any inert solvent for the reactant may be employed.

After the addition reaction is completed, the bulk of the solvent is removed by vacuum distillation, the Grignard adduct dissolved in a suitable solvent such as benzene, and hydrolyzed by the addition of water or ammonium chloride solution with cooling. The product is recovered by evaporation of the solvent after the removal of any residual inorganic material by filtration.

Conversion of the carbinol to the corresponding 5-(3- tertiary aminopropylidene) derivative (Step B) is effected by dehydration. The dehydration may be efifected in conventional manner employing such commonly used dehydrating agents as acetyl chloride, acetic anhydride or thionyl chloride. The alcohol may be dehydrated directly or may be first converted to a salt such as the hydrochloride, hydrobromide or sulfate. Conversion to the salt prior to dehydration may be preferable in some cases. The reaction may be carried outzat elevated temperatures, and in an excess of dehydrating agent or a solvent such as chloroform or glacial acetic acid may be employed. The desired product is recovered after rendering the mixture alkaline by extraction with a suitable solvent, and then removing the solvent.

Conversion of the compound obtained from Step B to the corresponding trans 10,1l-dihydroxy compound (Step C) is effected by hydrolyzing the former in an inert solvent, preferably at elevated temperatures, and in the presence of an acidic catalyst such as, for example, p-toluenesulfonic acid, concentrated sulfuric acid, trifiuoroacetic acid, dry hydrochloric acid and the like. Any number of inert solvents may be utilized, but it is preferred to employ a lower alkanol such as methanol, ethanol, isopropanol and the like. Where the product is insoluble in the solvent employed, it may be recovered by filtration and washed free of any residual acid and further purified by conventional methods. Where the product is soluble in the solvent employed, it may be recovered by evaporation of the solvent, diluting with water, neutralizing any residual acid with sufiicient alkali to render the medium basic and collecting the residue by conventional methods.

The trans 10,1l-dihydroxy compounds represented by structural Formula II may be prepared from the corresponding 5 (3-dialkylaminopropylidene) compound obtained in Step B above. In carrying out the process, it is preferred that the alkyl substituents attached to the nitrogen atom be the same. This is readily accomplished by appropriate selection of the Grignard reagent used to pre pare the carbinol from which the tertiary aminopropylcne compound is derived. This process may be illustrated as follows:

Haloformate HaICOOR Step D Hydrolysis X i X Step E iJHCH2CH2N O RH RI O O I Hydrolysis X Step 0 HCHzOHzNHR HO OH wherein Hal, X, X, R, R" and R are as previously defined and R"" is alkyl, aralkyl and aryl. However, it will be readily appreciated by those skilled in the art that inasmuch as the R"" substituent is removed during the dealkylation step, the selection of the particular haloformate will be limited only by its availability and subsequent ease of hydrolysis of the intermediate urethane produced.

Step D of the above process involves the condensation of the tertiary amino compound with a haloformate to form the corresponding urethane intermediate. While the reaction can be carried out in the absence of a solvent, it is preferable to employ a solvent. Suitable solvents include the aromatic hydrocarbons such as benzene and toluene, aliphatic hydrocarbons such as heptane and hexane, and the halogen hydrocarbons such as chloroform and carbon tetrachloride. The reaction may be carried out at room temperature, although an elevated temperature is preferred. At the conclusion of the reaction, the urethane is recovered, after removal of impurities, by evaporation of the solvent.

The urethane intermediate thus produced is then subjected to hydrolysis (Step E). The hydrolysis preferably may be carried out under basic conditions. After completion of the hydrolysis, the desired product is recovered in conventional manner, such as by extraction into a suitable solvent and evaporation of the solvent. Conversion to the corresponding 10,11-dihydroxy compound is accomplished using the procedure outlined in Step C.

Alternatively, the dealkylation may be accomplished by treatment of the tertiary aminopropylidene compound with a cyanogen halide to form the corresponding cyanamide intermediate, and the cyanamide thus produced hydrolyzed to the corresponding secondary amine. This process may be illustrated as follows:

RI/ R!!! Ha1-CN X X HCHzCHaNCR);

RI! R!!! Hydrolysis X X (iHCHzCHzN RI! R! O O I Hydrolysis X X Step 0 CHCHzCHzNHR HO OH X I X HCH2CH2NHR The tertiary amine is dissolved in a nonhydroxylic solvent such as benzene or ether and the solution slowly added to a solution of cyanogen halide in the same solvent, while stirring and permitting the alkyl halide to escape. After the reaction is complete, the basic material is separated by washing with dilute acid and the cyanamide isolated by evaporating the solvent. The cyanamide is hydrolyzed to the secondary amine in an alkaline medium, and the product recovered in conventional manner. Conversion to the corresponding 10,1l-dihydroxy compound is accomplished using the procedure outlined in Step C.

The process for the preparation of the cis 10,11-dihydroxy compounds of structural Formula I may be illustrated as follows:

A00 0A0 HaLMgCH2CHzOH2N R! X X Hydrolsis Step A wherein Hal, X, X, R and R are as previously defined and Ac represents acyl.

The starting compound, wherein X and X are both hydrogen and Ac is acetyl, may be prepared in the manner described by J. Rigaudy and L. Nedelec, Bull. Soc. Chim., France (1960), pgs. 400-405. Those starting compounds, wherein at least one of X and X' is other than hydrogen, may be prepared from the corresponding nuclearly substituted SH-dibenzo[a,d]-cyclohepten--one utilizing the procedure of J. Rigaudy et al. previously mentioned. Those starting compounds, wherein Ac is other than acetyl, may be prepared from the corresponding diol by treatment with an appropriate acylating agent following the procedure described by J. Rigaudy et al., above cited, for the preparation of the 10,11-diacetoxy derivative.

The preparation of the Grignard reagent, the reaction with the Grignard reagent (Step A), and dehydration of the resulting carbinol (Step B), may be carried out as previously described herein. However, the hydrolysis of the 10,11-diacyloxy compound to the corresponding cis 10,11-dihydroxy compound differs from that described for the preparation of the trans 10,1l-dihydroxy compounds in that the hydrolysis is effected under alkaline conditions such as by the use of potassium hydroxide and the like. Recovery of the product can be accomplished as described in Step C above, except that neutralization with alkali is unnecessary.

An alternate method for the preparation of the cis 10,11-dihydroxy compounds represented by structural formula I may be illustrated as follows:

X YEX This process involves treating a 5-(3-tertiary aminopropylidene)-5H-dibenzo[a,d]cycloheptene with an equimolar amount of osmium tetroxide and then hydrolyzing the resulting osmic ester. The reaction with the tetroxide is preferably carried out at room temperature and in a dry, inert solvent in which the osmium tetroxide is soluble. A particularly suitable solvent is dry benzene. Preferably, a catalyst is employed to facilitate the reaction, and pyridine is suitable for this purpose. After completion of the reaction, which may take several days or more, the osmic ester which precipitates out may be recovered by filtration. Hydrolysis of the ester to the desired product is conveniently effected in an aqueous, inert organic solvent such as an aqueous alkanol, preferably ethanol. The hydrolysis is preferably carried out at reflux temperature and in the presence of a suitable reducing agent such as sodium sulfite. The reducing agent is employed for the purpose of recovering the osmium which precipitates out in metallic form. After removal of the metallic osmium by filtration, the product is readily recovered in conventional manner.

The 5-(3-tertiary aminopropylidene)-5H-dibenzo[a,d] cycloheptene employed in the process may be readily obtained by treating the appropriately substituted SI-I-dibenzo[a,d]cycloheptene-S-one with a Grignard reagent, namely, tertiary aminopropyl magnesium halide, hydrolyzing the resulting Grignard adduct to form the corresponding carbinol and dehydrating the latter, as described in the literature.

The preparation of the cis 10,11-dihydroxy compounds represented by structural formula II may be accomplished by dealkylating the corresponding cis 10,11-diacyloxy-5- (3-dialkylaminopropylidene) derivative in the same manner as described for the dealkylation of the trans 5-(3- dialkylaminopropylidene) derivative, as described in Steps D and E above. This process may be illustrated as follows:

Ag? 0 A. c

Haloformate HalCOOR x i Step D CHCHzCH:

/R CHCHz CHzN O Hydrolysis I p E uu HO OH HCH: CHzN wherein Ac, Hal, R, R", X and X are as previously defined.

It should be noted that the alternate method of dealkylation mentioned hereinabove for the preparation of the trans 10,11-dihydroxy compounds of structural Formula II cannot be used for the preparation of the cis 10,11-dihydroxy compounds of Formula II.

It will be readily appreciated by those skilled in the art that the compounds represented by structures I and II, in addition to the element of geometric isomerism determined by the relationship of the hydroxyls to each other, possess a second element of geometric isomerism when the dibenzocycloheptene nuclet is unsymmetrically substituted, depending on the position of the propylidene side chain relative to the nuclear substituent(s).'

The separation of these isomers can be achieved by conventional techniques. While the mixture of such' isomers possess pharmacological activity, in some instances the activity may be greater in one pure isomer than the other.

Inasmuch as the compounds of this invention may exist as geometric isomers with respect to the hydroxyl substituents only or with respect to both the hydroxyl substituents and the propylidene side chain, the following procedure for designating the isomers hereinabove and in the examples and claims which follow has been employed. Where isomers exist only with respect to the hydroxyl substituents, the designation of the particular isomer precedes the name of the compound. Where isomers exist as to both the hydroxyl substituents and the propylidene side chain, the designation of the isomers immediately precedes the substituent to which it refers. In those instances where isomers exist with respect to both the hydroxyl substituents and the propylidene side chain and the isomers of the latter have not been separated, then only the designation of the isomer with respect to the hydroxyl substit-uents is given and such designation precedes the name of the compound. However, where no designation of isomers is specified with respect to the compounds of this invention, it is to be understood that all possible stereoisomers are included.

The preparation of representative compounds encompassed within the scope of the present invention is described in the following examples which are illustrative only and are not to be construed as in any way limiting the scope of the invention.

EXAMPLE 1 Trans 311,126 dihydro 2,2-dimethyl-8-(3-dimethylaminopropyl) 8 hydroxy 8H dibenzo[3,4:6,7]cyclo hepta[1,2-d]-1,3-dioxole 3-dimethylaminopropylmagnesium chloride is prepared from magnesium turnings (4.05 g., 0.166 g. atom) and 3- dimethylaminopropyl chloride (20.2 g., 0.166 mole) in 150 ml. of dry tetrahydrofuran, following the method of US. Patent No. 3,046,283. In a nitrogen atmosphere, a solution of trans 304,125 dihydro-2,2-dimethyl-8H-dibenzo- [3,426,7]cyclohepta-[1,2-d]-1,3-dioxol 8 ene (23.2 g., 0.083 mole) in 100 ml. of dry tetrahydrofuran is added dropwise to the stirred solution of the Grignard reagent while cooling in an ice-bath. The mixture is allowed to come to room temperature and stirred for 2 hours. The bulk of the solvent then is distilled below 50 C. under reduced pressure. The residue is dissolved in 150 ml. of benzene and water, 20 ml., is added dropwise with stirring and cooling. The benzene layer is decanted from the gelatinous precipitate which then is extracted with four 100 ml. portions of boiling benzene. The combined benzene extracts are Washed with water and extracted with three 100 ml. portions of 0.5 M. citric acid. The acid extract is made basic with sodium hydroxide, and the oily base that separates is extracted into benzene. After washing the combined extracts with water and drying over anhydrous sodium sulfate, the benzene is evaporated and the product obtained as a viscous yellow oil in a yield of 29.5 g. (96%).

The base may be converted to the hydrogen oxalate salt by treating an ethereal solution with a solution of oxalic acid excess) in isopropyl alcohol. The trans 30:,12/3 dihydro 2,2 dimethyl 8 (Ii-dimethylaminopropyl) 8 hydroxy 8H dibenzo[3,4:6,7]cyclohepta- [1,2-d]-1,3-dioxo1e hydrogen oxalate is obtained as a white crystalline solid, M.P. 169-172 C., dec. Repeated recrystallizations from mixtures of isopropyl alcohol and absolute ether give the product, M.P. 171173 C., dec.

Analysis.Calcd for C H NO -C H O (percent): C, 65.62; H, 6.83. Found (percent): C, 65.08; H, 6.72.

EXAMPLE 2 Following the procedure of Example 1, the products enumerated below are obtained using the ketone of Example 1 and the Grignard reagent designated below.

Grignard reagent Product 3-diethylaminorpopylmagnesium chloride.

3-(1-pyrrolidyl)-propylmagnesium chloride.

3-(l-piperldyl)-propylmagnesium chloride.

3-(1-ethyl-4-piperazinyl)-propylmagnesium chloride.

3-(4-morpholinyl)-proDY magesium chloride.

3-(N-ethyl-N-methylamino)- propylmagncsium chloride.

EXAMPLE 3 Following th procedure of Example 1, the products enumerated below are obtained using the Grignard reagent of Example 1 and the ketone designated below.

Ketcne Trans 3a,12 3-dihydrc-2,2-

dimethyl-6-dirnethylsulfamoyl- 8H-dlbenzc-[3,4:6,7]cyclohepta [1,2-d]-1,3-dioxol-8-one.

Product EXAMPLE 4 Trans 3o ,l2,B-dihydro-2,2-dimethyl-8-(33-dimethylaminopropylidene) 8H dibenzo[3,4,6,7]cyclohepta[1,2]-

1 ,3-dioxole A solution of trans 3a,l2fl-dihydro-2,2-dimethyl-8-(3 dimethylaminopropyl) 8 hydroxy-8H-dibenzo[3,4:6,7] cyclohepta[1,2-d]-1,3-dioxole (1.3 g., 0.00354 mole) in 15 ml. of acetic anhydride is heated to refluxing for 4 hours.-

extracted into benzene. The washed benzene extract is evaporated under reduced pressure, leaving the product as an oily residue weighing, typically, 950 mg. Treatment of an ethereal solution of the base with a solution of 300 mg. of oxalic acid in 3 ml. of isopropyl alcohol precipitates trans 3a,12;3 dihydro-2,2-dimethyl-8-(3-dimethylaminopropylidene) 8H-dibenzo[3,4:6,7]cyclohepta[l,2-d]-1,3- dioxole hydrogen oxalate, M.P. 204-206 C., dec., in a yield of 1.05 g. (67.5% The pure product from another experiment melts at 205-206 C., dec., after recrystallization from isopropyl alcohol.

Analysis.-Calcd for C H NO -C H O (percent): C, 68.32; H, 6.65; N, 3.19. Found (percent): C, 68.36; H, 6.72; N, 3.15.

EXAMPLE 5 Following the procedure of Example 4, the products enumerated below are obtained employing the products enumerated in Examples 2 and 3 in place of the dioxole used in Example 4.

trans 8- 3-diethylaminopropylidene -3 a,12B-dihydro-2,2- dimethyl-8H-dibenzo[3,4:6,7]cyclohepta[1,2-d]-1,3- dioxole trans 3[1,1ZB-dihydro-2,2-dimethyl-8- 3- 1-pyrrolidyl)- propylidene1-8H-dibenzo[3,4:6,7]cyclohepta[1,2-d]- 1,3-dioxole trans 311,125-dihydro-2,2-dimethyl-8-[3-(1-piperidyl-propylidene]-8lH-dibenzo[3,4:6,7]cyclohepta[1,2-d]-1,3- dioxole trans 3 a,12,8-dihydro-2,2-dimethyl-8-[3-(1-ethyl-4-piperazinyl -propylidene]-8H-dibenzo [3 ,4: 6,7 cyclohepta [1,2-d]-1,3-dioxole trans 3a,12fl-dihydro-2,2-dimethyl-8-[3,(4-morpholinyl)- propylidene1-8H-dibenzo[3,4: 6,7] cyclohepta[ 1,2-d]- 1,3-dioxole trans 3 a,12,3-dihydro-2,2-dimethy1-8-[3-(N-ethyl-N- methylamino)-propylidene] -8H-dibenzo [3 ,4 6,7] cyclohepta[1,2-d]-1,3-dioxole trans 3a,12fi-dihydro-8-(3-dimethylaminopropylidene)- 8H-dibenzo[3,4:6,7]cyclohepta[1,2-d]-1,3-dioxole trans 3a,12[3-dihydro-8-( 3-dimethylaminopropylidene)-2- phenyl-SH-dibenzo[3,4:6,7]cyclohepta[1,2-d]-1,3- dioxole trans 3 a,12B-dihydro-8-(3-dimethylaminopropylidene)-2- methyl-8H-dibenzo [3 ,4:6,7] cyclohepta 1,2-d)-1,3- dioxole trans 2-benzyl-3 a,12,8-dihydro-8- (3-dimethylarninopropylidene-8H-dibenzo [3,4: 6,7 cyclohepta[ 1,2-d] -1,3- dioxole trans 3 a,1ZB-dihydro-8-(3-dimethylaminopropylidene)-2- ethyl-Z-methyl-SH-dibenzo 3 ,4: 6,7]cyclohepta[1,2-d]- 1,3-dioxole trans 3 a, l2,6-dihydro-2,2-dimethyl-8- 3-dimethylaminopropylidene -6-methylsulfonyl-SH-dibenzo [3,4: 6,7] cyclohepta[1,2-d]-1,3-dioxole trans 6-chloro-3a,12fi-dihydro-2,2-dimethyl-8- (3-dimethylaminopropylidene)-8H-dibenzo [3 ,4:6,7] cyclohepta [1,2-d] -1,3-dioxole trans 3 a,12/3-dihydro-2,2-dimethyl-8-(3-dimethylaminopropylidene -6-dimethylsulfamoyl-SI-I-dibenzo 3,4: 6,7]-eyclohepta[1,2-d]-1,3-dioxole EXAMPLE 6 Trans 10,11 dihydro 10-11 dihydroxy-5-(3-dimethylaminopropylidene -5H-dibenzo [a,d] cycloheptene A solution of trans 3a,125-dihydro-2,2-dimethyl-8-(3- dimethylaminopropylidene) 8H dibenzo [3,4:6,7] cyclohepta[1,2 d] 1,3 dioxole (350 mg, 0.001 mole) and p-toluenesulfonic acid monohydrate (230 mg. 0.0012 mole) in 35 ml. of absolute methanol is heated to reflux for 4 hours. The cooled solution is neutralized with 1 ml. of 1 M potassium hydroxide in methanol and then the solvent is distilled under reduced pressure. The residue is partitioned between benzene and water and the aqueous layer re-extracted twice with benzene. The combined benzene extracts are washed with water and then evaporated to dryness under reduced pressure. Trituration of the residue with absolute ether yields the product as a white crystalline solid, M.P. 132.5134.5 C., weighing 230 mg. (74.5%). After purification by sublimation and crystallization from a mixture of ethanol and water, an analytical sample melts at 134.5136.5 C.

Analysis.Calcd for C H NO (percent): C, 77.64; H, 7.49; N, 4.53. Found (percent): C, 77.59; H, 7.42; N, 4.47.

EXAMPLE 7 Following the procedure of Example 6, the products enumerated below are obtained using the products enumerated in Example 5 in place of the dioxole used in Example 6.

trans 5-(3-diethylaminopropylidene) 10,11-dihydro- 10,1l-dihydroxy-SH-dibenzo[a,d]cycloheptene trans 10,1l-dihydro-10,11-dihydroxy-5-[3-(l-pyrrolidyl)- propylidene1-5H-dibenzo [a,d] cycloheptene trans 10,11-dihydro-10,11-dihydroxy-5-[3-(1-piperidyl)- propylidene1-5H-dibenzo [a,d] cycloheptene trans 10,11-clihydro-10,11dihydroxy-5-[3-(1-ethyl-4- piperazinyl)-propylidene]-5H-dibenzo [a,d] cycloheptene trans 10,11-dihydro-10,1l-dihydroxy-S-[3-(4-morpholinyl)-propylidene]-5H-dibenzo [a,d] cycloheptene trans 10, l l-dihydro- 10,1 1 -dihyclroxy-5- [3- (N-ethyl-N- methylamino)-propylidene]-5H-dibenzo[a,d] cycloheptene trans 10,11-dihydro-l0-1l-dihydroxy-S-(3-dimethylaminopropylidene)-5H-dibenzo[a,d1cycloheptene trans 10,1l-dihydro-10,1l-dihydroxy-S-(3-dimethylaminopropylidene -3-methylsulfonyl-SH-dibenzo [a,dJcycloheptene trans 3-chloro-10,l l-dihydro-IO,11-dihydroxy-5-(3-dimethylaminopropylidene)-5H-dibenzo [a,d] cycloheptene trans 10,1l-dihydro-10,1 l-dihydroxy-S-(3-dimethylaminopropylidene)-3-dimethylsulfamoyl-5H- dibenzo [a,dlcycloheptene EXAMPLE 8 Trans 8-[3-(N-cyano N methylamino)-propylidene]- 30:,12/3 dihydro 2,2 dimethyl-SH-dibenzo[3,4:6,7] cyclohepta[1,2-d]-1,3-dioxolc In a system protected by a drying tube, and in which a nitrogen atmosphere is maintained, a solution of trans 30,125 dihydro 2,2 dimethyl-8-(3-dimethylaminopropylidene) 8H dibenzo[3,4:6,7]cyclohepta[1,2-d]- 1,3-dioxole (2.25 g., 0.00645 mole) in 12 ml. of dry benzene is added dropwise over a 30 minute period to a stirred solution (1.85 ml.) of 4.25 M cyanogen bromide in benzene. Stirring is continued for 1 /2 hours and the mixture then allowed to stand at room temperature overnight. Solvent and excess cyanogen bromide are evaporated under reduced pressure and the residue dissolved in benzene. The solution is washed with water, dilute citric acid, then with water, and evaporated to dryness under reduced pressure. The trans 8-[3 (N cyano-N- methylamino)-propylidene) 311,126 dihydro 2,2 dimethyl 8H dibenzo[3,4:6,7]cyclohepta[1,2-d] 1,3-dioxole is obtained as a yellow oily residue, weighing 1.8 g. (78%).

EXAMPLE 9 Following the procedure of Example 8, the products enumerated below are obtained employing the 8-(3-dialkylaminopropylidene) products enumerated in Example 5 in place of the dioxole used in Example 8.

trans 8-[3-(N-cyano-N-ethylamino)-propylidene]-3a,

12/i-dihydro-2,2-dimethyl-8H-dibenzo[3,416,71 cyclohepta[1,2-d]-1,3-di0xole trans 8- 3- (N-cyano-N-methylaminopropylidene] 3oz,12[3-dihydro-8H-dibenzo[3,4:6,7]cyclohepta [1,2-d]-1,3-dioxole trans 8- [3- (N-cyano-N-methlamino)-propylidene]- 3a,12/i-dihydro-2-phenyl-SH-dibenzo[3,4: 6,7] cyclohepta 1,2-d1- 1,3-dioxole trans 8-[3-(N-cyano-N-methylamino)-propylidene]- 3m,12 8-dihydro-2-methyl-8H-dibenzo[3,4: 6,7] cyclohepta[1,2-d]-1,3-dioxole trans 2-benzyl-8- 3- (N-cyano-N-methylamino) propylidene] -3a,12fi-dihydro-8H-dibenzo [3,4: 6,7 cyclohepta[1,2-d]-1,3-dioxole trans 8-[3- (N-cyano-N-methylamino)-propy1idene]- 3a,12B-dihydro-2-ethyl-2-methy1-8H-dibenzo [3,4:6,7]cyclohepta[1,2-d]-1,3-dioxole trans 8- 3- (N-cyano-N-methylamino) -propy1idene] 3a,1ZQ-dihydro-LZ-dimethyl-6-methylsulfonyl-8H- dibenzo[3,4:6,7]cyclohepta[1,2-d]-1,3-dioxole trans 6-chloro-8- [3- (N-cyano-N-methylamino)propylidene]-3a,12p-dihydro-2,2-dimethyl-8H-dibenzo [3,4:6,7]cyclohepta[1,2-d]-1,3-dioxole trans 8- 3- (N-cyano-N-methylamino) -propylidene] 3a,12,8-dihydro-Z,2-dimethyl-6-dimethylsulfamoyl- 8H-dibenzo[3,4:6,7]cyclohepta[1,2-d]-1,3-dioxoie EXAMPLE 10 Trans 301,125 dihydro-2,2-dimethyl-8-(3-methylaminopropylidene) 8H dibenzo[3,4:6,7]cyclohepta[1,2-d]- 1,3-dioxole The oily cyanamide (1.44 g., 0.004 mole) prepared as in Example 8 above, is dissolved in a solution of potassium hydroxide (1.12 g., 0.02 mole) in 12 m1. of n-butyl alcohol and the solution is heated to refluxing in a nitrogen atmosphere for 12 hours. The solvent is distilled under reduced pressure and the residue partitioned between hexane and water. After two re-extractions of the aqueous layer with hexane, the combined hexane extracts are washed with water and extracted with 50 ml. of 0.1 M citric acid. The acid extract is rendered alkaline with sodium hydroxide and the oily base extracted into benzene. The washed and dried benzene extract is evaporated to dryness under reduced pressure, leaving the product as an oily residue weighing, typically, 920 mg.

The base may be converted to the hydrogen oxalate salt by treating an ethanolic solution with a solution of oxalic acid (10% excess) in absolute ethanol. Analytically pure trans 3a,12,8-dihydro-2,2-dimethyl-8-(3-methylaminopropylidene)-8H dibenzo [3,4:6,7]cyclohepta- 1,2-d]-1,3-dioxole hydrogen oxalate from another experiment melts at 224 C., dec., after repeated recrystallizations from absolute ethanol.

Analysis.-Calcd for C H NO -C HgO (percent): C, 67.75; H, 6.40; N, 3.29. Found (percent): C. 67.78; H, 6.32; N, 3.41.

Conversion of the oily base (900 mg.) to the p-toluenesulfonate salt by treating an ethereal solution with a solution of p-toluene sulfonic acid monohydrate excess) in absolute ethanol, affords the white crystalline salt, M.P. 148-150" C., dec., in a yield of 950 mg.

EXAMPLE 11 Following the procedure of Example 10, the products enumerated below are obtained employing the products enumerated in Example 9 in place of the cyanamide used in Example 10.

trans 304,12 3-dihydro12,2-dimethyl-8-(3-ethylaminopropylidene )-8H-dibenzo [3,4: 6,7] cyclohepta[ 1,2-d1- 1,3-dioxole trans 3u,12b-dihydro 8-(3 methylaminopropylidene)- SH-dibenzo 3,4: 6,7 cyclohepta[ 1,2-d] -1,3-dioxole trans 3a,12b-dihydro-8-(3-methylaminopropylidene)- 2-phenyl-8H-dibenzo[3,4:6,7]cyclohepta[1,2-d]-1,3- dioxole a trans 3a,12fi-dihydro-2-methyl-8-(3-methy1aminopropylidene -8H-dibenzo 3 ,4: 6,7] cyclohepta[ 1,2-d]-1,3- dioxole trans 2-benzyl-3 oz, IZ/R-dihydro-S- 3-methylaminopropylidene)-8H-dibenzo[3,4:6,7]cyclohepta[1,2-d]-l,3- dioxole trans 3 a,125-dihydro-2-ethyl-2-methy1-8-(3-methylaminopropylidene -8H-dibenzo 3 ,4: 6,7]cyclohepta[ 1,2-d] 1,3-dioxole trans 3 cc, 1Zfl-dihydro-Z,Z-di'methyl-8- 3-methylaminopropylidene -6-methylsulfonyl-SH-dibenzo 3,4: 6,7 cyclohepta[1,2-d]-1,3-dioxole trans 6-Chl010-3a, 12fi-dihydro-2,2-dimethyl-8- (Ii-methylaminopropylidene) -8H-dibenzo[ 3,4 6,7] cyclohepta- [1,2-d]-1,3-dioxole trans 3a,1Z/S-dihydro-2,2-dimethyl-6-dimethylsulfamoyl- 8- 3-methylaminopropylidene -8H-dibenzo 3,4 6,7] cyclohepta[ 1,2-d] 1 ,3-dioxole EXAMPLE 12.

Trans 10,1 l-dihydro-lO; 1 l dihydroxy-S-(3-methylaminopropylidene)-5H-dibenzo [a,d]cycloheptene A solution of trans 3a,12/3-dihydro-2,2-dimethyl-8-(3- methylaminopropylidene) 8H dibenzo [3,4:6,7]cyclohepta[1,2-d] 1,3 dioxole ptoluenesulfonate (700 mg., 0.00138 mole) and p-toluenesulfonic acid monohydrate (60 mg., 0.000316 mole) in 60 ml. of absolute methanol is heated to refluxing for 4 hours. The cooled solution is neutralized with 1.5 ml. of 1 M potassium hydroxide in methanol and then the solvent is distilled under reduced pressure. The residue is partititioned between benzene and water and the aqueous layer re-extracted with benzene. The combined benzene extracts are washed with Water and then evaporated to dryness under reduced pressure, leaving the product as an oily solid residue. Sublimation of the product at 142 C. and 0.1 mm. aifords White crystals, M.P. 153155 C., weighing, typically, mg.

(30%). An analytical sample is obtained by crystallization from a mixture of ethanol and water and resublimation, and melts at l54-156 C.

Analysis.-Calcd for C H2 NO (percent): C, 77.26; H, 7.17; N, 4.74. Found (percent): C, 77.48; H, 7.12; N, 4.77.

EXAMPLE 13 Cis 10,1i1-diacetoxy-10,1 1-dihydro-5-(3-dimethylaminopropyl) -5-hydroxy-5H-dibenzo [a,d] cycloheptene 3-dimethylaminopropylmagnesium chloride is prepared from magnesium turnings (4.86 g., 0.2 g. atom) and 3-dimethylaminopropyl chloride (24.3 g., 0.2. mole) in 75 ml. of dry tetrahydrofuran following the method of US. Patent No. 3,046,283. In a nitrogen atmosphere, the solution of the Grignard reagent is added dropwise to a stirred suspension of cis 10,1l-diacetoxy-10,1l'dihydro- SH-dibenzo[a,d]cyclohepten-5-one (30.0 g., 0.0925 mole) in 60 ml. of tetrahydrofuran while cooling in an ice-bath. The mixture is stirred in the cold for 2 hours and the bulk of the solvent then is distilled below 50 C. under reduced pressure. The residue is dissolved in benzene and water, 30 ml., is added with stirring and cooling. The benzene is decanted and the gelatinous precipitate washed by decantation with boiling benzene. The combined benzene extracts are extracted repeatedly with 0.5 M citric acid. The acid extract is rendered alkaline with sodium hydroxide and the oily base extracted into benzene. Evaporation of the washed and dried benzene extract under reduced pressure leaves a yellow glass which is extracted into 1 l. of cyclohexane. The solution is filtered from insoluble material and the solvent evaporated. Crystallization of the residual solid from a mixture of ether and hexane gives a first crop of product, M.P. 135-136 C., weighing 12.4 g. A second crop of 8.1 g., M.P. 132134 C., is obtained from the mother liquor. An analytical sample melts at 134135 C. after recrystallization from a mixture of ether and hexane.

Analysis.--Calcd for C H NO (percent): C, 70.05; H, 7.10; N, 3.40. Found (percent): C, 70.23; H, 7.09; N, 3.37.

EXAMPLE 15 Following the procedure of Example 14, the products enumerated below are obtained employing the ketone of Example 14 and the Grignard reagent designated below.

Product Cis 10,11-diacetoxy-fi-O-diethyiaminopropyl)-10,11-dihydro-5- hydroxy-SI-I-dibenzo [a,d]eyeloheptene.

Cis 10,11-diaeetoxy-1OJl-dihydro- 5-[3-(1-ethyl-4-piperazinyl)- propyll-S-hydroxy-SH-dibenzo [a,dleyeloheptene.

Cis l0,11-diaeetoxy'10,1l-dihydro- 5-[3-(N-ethyl-N-methylamino)- propyl]-5-hydroxy-5H-dibenzo [a,d]cyeloheptene.

EXAMPLE 16 Following the procedure of Example 14, the products enumerated below are obtained employing the Grignard reagent of Example 14 and the ketone designated below.

Grignard reagent 3-diethylaminopropylmagnesium ehlori e.

3-(1-pyrrolidy1)-propylmagnesium chloride.

3-(1-piperidyl)-propylmagnesium chloride.

3-(1-ethyl-4-piperazinyl)-propylmagnesium ehlori e.

3-(4 m0rpholinyl)-propylmagnesium chloride.

3-(N-ethyl-N-methylamino)- propylmagnesium chloride.

Kctone Cis 10,11-dibutyryloxy-10,11-

dihydro-5H-dibcnzo-[e,d]eyclohepten-5-one.

Cis 10,11-dicaproyloxy-10,1I-dihydro-SH-dibe11zo-[a,d]eyelohepten-5-one.

Cis 3-ehloro-10,11-diaeetoxy-10,11- (1ihydro-SH-dibenzo[a,d]cycl0- heptenJS-one.

Cis 10,1l-diaeetoxy-10,11-dihydro-3- mothyhsulfonyl-SH-dibenzo [a,d]-eyelohepten-5-one.

Cis 10,1l-diacetoxy-IO,ll-dihydro- 3-dimethyl-suliamoyl-5II-dihenzo [a,d]-cyelohepten-5-one.

Product EXAMPLE 17 Cis 10,11-diacetoxy-10,11-dihydro-5-(Za-dimethylaininopropylidene)-5H-dibenzo[a,d]cyc1oheptene A solution of cis 10,1l-diacetoxy-10,1l-dihydr0-5-(3- dimethylaminopropyl) 5 hydroxy 5H dibenzo[a,d] cyclohepten (19.5 g., 0.0475 mole) in 300 ml. of acetic anhydride is heated to refluxing for 4 hours. The solution is evaporated to dryness under reduced pressure and the residual oil partitioned between 0.5 M citric acid and benzene. After repeated washing with benzene, the aqueous acid layer is rendered alkaline with sodium hydroxide and the oily base extracted into benzene. Evaporation of the washed and dried benzene extract leaves the product as an oily residue weighing, typically, 18.0 g.

The base may be converted to the hydrogen oxalate salt by treating an ethanolic solution with a solution of oxalic acid (10% excess) in absolute ether. Cis 10,11- diaeetoxy-10,11-dihydro-5 (3 dimethylaminopropylidene) 5H dibenzo[a,d]cycloheptene hydrogen oxalate precipitates as a white crystalline solid which melts at 165-166 C. after one recrystallization from a mixture of absolute ethanol and absolute ether.

Analysis.-Calcd for C H NO -C H O (percent): C, 64.58; H, 6,05; N, 2.90. Found (percent): C, 64.31; H, 5.84; N, 2.79.

EXAMPLE 18 Following the procedure of Example 17, the products enumerated below are obtained employing the products enumerated in Examples 15 and 16 in place of the dibenzocycloheptene used in Example 17.

cis 10,1l-diacetoxy-S-(3-diethylaminopropylidene)- 10,1l-dihydro-SH-dibenzo[a,djcycloheptene cis 10,11-diacetoxy-10,11-dihydro-5-[3-(1-pyrrolidyl)- propylidene] -5H-dibenzo a,d] cycloheptene cis 10,11-diacetoxy-10,1l-dihydro-5-[3-(1-piperidyl)- propylidene -5H-dibenzo [a,d] cycloheptene cis 10,1 1-diacetoxy-10,11-dihydro-5-[3(1-ethyl-4-piperazinyl propylidene] -5H-dibenzo [a,d] cycloheptene cis 10,11-diacetoxy-10,1l-dihydro-S-[3-(4-morpholinyl)- propylidene] -5H-dibenzo a.d cycloheptene cis 10,11-diacetoxy-10,1l-dihydro-S-[3-(N-ethyl-N- methylamino -propylidene]-5H-dibenzo a,d] cycloheptene cis 10,11-dihydro-5-(3-dimethylaminopropylidene)-10,11-

dipropionyloxy-SH-dibenzo a,d cycloheptene cis 10,11-dibutyryloxy-10,1l-dihydro-S-(3-dirnethylaminopropylidene -5H-dibenzo [a,d] cycloheptene cis 10,11-dibenzoyloxy-10,11-dihydro5-(3-dimethylaminopropylidene -5H-dibenzo a,d] cycloheptene cis 10,11-dicaproyloxy-10,11-dihydro-5-(3-dimethylaminopropylidene) -5H-dibenzo [a,d] cycloheptene cis 3-chloro-10,11-diacetoxy-10,11-dihydro-5-(3-dimethylaminopropylidene -5H-dibenzo a,d] cycloheptene cis 10,11-diacet0xy-10,11-dihydro-5-(3-dimethylaminopropylidene)-3-methylsulfonyl-SH-dibenzo[a,d] cycloheptene cis 10,11-diacet0xy-10,11-dihydro-5-(3-dimethylaminopropylidene)-3-dimethylsulfamoyl-SH-dibenzo[a,d]- cycloheptene EXAMPLE 19 Cis 10,11-dihydro 10,1 1-dihydroxy-5-(3-dimethylan1inopropylidene -5H-dibenzo a,d] cycloheptene A solution of cis 10,11-diacetoxy-10,11-dihydro-5-(3- dimethylaminopropylidene) 5H dibenzo[a,d] cycloheptene (1.6 g., 0.00417 mole) and potassium hydroxide (1.6 g., 0.024 mole) in 70 ml. of absolute methanol is heated to refluxing for 15 minutes. The solvent is evaporated under reduced pressure and the residue treated with 50 ml. of water. The precipitate is collected, washed with water, and recrystallized from a mixture of ethanol and water to obtain the product as a white crystalline solid, M.P. 173175 C., weighing 1.05 g. (81%). A purified sample from another experiment melts at 171-174 C.

after sublimation at C. and 0.05 mm.

Haloformate Product Benzyl chloroformate Trans 8-[3-(N-earbobenzoxy-N- methylamino)-propylidene]- 3a,-12fl-dihydro-2,2-dimethyl-8H- dlbenzo[3,4:6,7] cyclohepte- Phenyl chloroiormate Trans 8-[3-(N-earbopenoxy-N- methylamino)-propylidene)-3a,- 12B-dihydro-2,2-dimethyl-8H- dibenzo[3,4:6,7]cyclohepta- Propyl chloroformate Trans 8-[3-(N-carbopropoxy-N- methylamino)-propylidene]- 3a,12B-dihydro-2,2-dimethyl- 8H-d1benzo[3,4:6,7] cyclohepte- [1,2-d]-1,3-dioxle.

EXAMPLE 26 Cis 10,1 l-dihydro-110,1 1-dihydroxy-5=(3-methy1aminopropyl)-5H-dibenzo[a,d1cycloheptene A solution of the oily urethane (2.8 g., 0.0076 mole) obtained in Example 21 and potassium hydroxide (2.5 g., 0.04 mole) in 25 ml. of n-butyl alcohol is stirred and heated to refluxing in a nitrogen atmosphere for 6 hours. The solvent is distilled under reduced pressure and the residue partitioned between benzene and water. After reextraction of the aqueous phase, the combined benzene extracts are Washed with water and then extracted with 15 ml. and ml. portions of 0.5 M citric acid. The acid extract is rendered alkaline with sodium hydroxide and the oily base extracted into benzene. The washed and dried benzene extract is concentrated to a small volume. The product separates as a white crystalline solid and is collected, washed with benzene, and dried to obtain 1.05 g. (47% 'M.P. 140-143 C. The pure product from another experiment melts at 143-145 C. after repeated crystallizations from benzene and from mixtures of ethanol and water.

Analysis.Calcd for C H NO (percent): C, 77.26; H, 7.17; N, 4.74. Found (percent): C, 77.34; H, 7.18; N,

EXAMPLE 27 Following the procedure of Example 26, the products enumerated below are obtained employing the products enumerated in Examples 22 and 23 in place of the urethane used in Example 26.

cis 10,1l-dihydro-10,1l-dihydroxy-S-(S-ethylaminopropylidene) -5H-dibenzo [a,d] cycloheptene cis 10,1 1-dihydro-10,1 l-dihydroxy-S- (3 methylaminopropylidene -5H-dibenzo [a,d] cycloheptene cis 3-chloro-10,1 1-dihydro-10,1 1-dihydroxy-5-(3-methylaminopropylidene)-5H-dibenzo [a,d] cycloheptene cis 10,1 1-dihydro-10,11-dihydroxy-5-(3-methylaminopropylidene) -3 -methylsulfonyl-SH-dibenzo [a,d] cycloheptene cis 10,1 1-dihydro-10,1 1-dihydroxy-3-diemthylsu1famoyl- 5- (S-methylaminopropylidene -5H-di=benzo [a,d] cycloheptene EXAMPLE 28 Following the procedure of Example 26, the products enumerated below are obtained employing the products enumerated in Examples 24 and 25 in place of the urethane used in Example 26.

trans 10,1 l-dihydro-10,1 1-dihydroxy-5-(3-ethylaminopropylidene -5H-dibenzo [a,d] cycloheptene trans 10,1 1-dihydro 10,1 1-dihydroxy-5-(3-methylaminopropylidene -5H-dibenzo [a,d] cycloheptene trans 3-chloro-10,1 1-dihyrdro-10,1 1-dihydroxy-5-(3- methylaminopropylidene) -5H-dibenzo [a,d] cycloheptene trans 10,1 1-dihydro-10,1 l-dihydroxy-S- (3-methylaminopropylidene -3 -methylsulfonyl-SH-dibenzo [a,d] cycloheptene 20 trans 10,1 1-dihydro-10,1 1-dihydroxy-3-dimethylsulfamoyl-S- 3-methylaminopropylidene) -5H-dibenzo [a,d] cycloheptene EXAMPLE 29 Cis 10,1 1-dihydro-10,1l-dihydroxy-S-(3-dimethylaminopropylidene) -5H-dibenzo [a,d] cycloheptene A solution of 5-(3-dimethylaminopropylidene)-5H-dibenzo[a,d]cycloheptene (1.06 g., 0.00386 mole) in 7 ml. of dry benzene and 0.6 ml. of dry pyridine is treated with a solution of osmium tetroxide (1.0 g., 0.00394 mole) in 6 ml. of dry benzene and the mixture allowed to stand at room temperature for 10 days. The solution is decanted from the black precipitate which separates and the solid washed once with 25 ml. of benzene by decantation. The benzene solution and washings are filtered through diatomaceous earth. The combined precipitate and diatomaceous earth are suspended in 60 ml. of ethanol and heated to refluxing for 45 minutes with 25 ml. of a saturated aqueous solution of sodium sulfite. After filtering the mixture through the diatomaceous earth, the filtrate is evaporated under reduced pressure until a dark oil separates. The residue is diluted with an equal volume of water and the oily base extracted into benzene. Evaporation of the washed and dried benzene extract leaves the product as an oily solid residue weighing 450 mg. Purification by sublimation at C. and 0.1 mm. and crystallization of the sublimate from a mixture of ethanol and water affords the product as a white crystalline solid, M. P. 172.5-175.5 C., in a yield of 250 mg. (20%).

Analysis.-Calcd for C H O N (percent): C, 77.64; H, 7.49. Found (percent): C, 77.41; H, 7.49.

What is claimed is:

1. A compound of the formula /R HCHzCHzN wherein R is a lower alkyl radical;

X and X are selected from the group consisting of hydrogen, halogen, loweralkyl sulfonyl and diloweralkyl sulfamoyl; and

R" and R are selected from the group consisting of hydrogen, loweralkyl, phenyl and benzyl.

2. 8-[3-(N-cyano N methylamino)-propylidene]-3oc, IZB-dihydro 2,2 dimethyl 8H dibenzo[3,4: 6-7]cyclohepta[ l,2-d]-l,3-dioxole.

3. Trans 8 [3-(N-dyano-N-ethylamino)-propylidene]- 3a, 1 213 dihydro-2,2-dimethyl-8H-dibenzo 3,4 6,7] cyclohepta[1,2-d]-1,3,-dioxole according to claim 1.

4. Trans 8-[3-(N-cyano N methylamino)-propylidene] 311,125 dihydro SH-dibenzo[3,4:6,7]cyclohepta [1,2-d]-1,3,-dioxole according to claim 1.

5. Trans 8[3-(N-cyano N methylamino) propylidene] 3a,12;9 dihydro-Z-phenyl-8H-diabenzo[3,426,7] cyclohepta[1,2-d]-1,3-dioxole according to claim 1.

6. Trans 8-[3-(N-cyano N methylamino)-propylidene] 311,125 dihydro-2-methyl 8H dibenzo[3,4:6,7] cyclohepta[1,2-d]-1,3-dioxole according to claim 1.

7. Trans 2-benzyl-8-[3-(N-cyano N methylamino)- propylidene] 30 12;? dihydro 8H dibenzo[3,4:6,7] cyclohepta[1,2-d]-1,3-dioxole according to claim 1.

8. Trans 8-[3-(N-cyano N methylamino) propylidene] 301,128 dihydro-Z-ethyl-Z-methyl 8H dibenzo- [3,4:6,7]cyclohepta[1,2-d] 1,3 dioxole according to claim 1. 

